A simple stability indicating RP-HPLC method for the analysis of Adapalene and Dapsone in pharmaceutical gel formulation was developed and validated. A gradient elution was performed on an analytical column Phenomenex Kinetex C8 (150 × 4.6 mm, 5 micron) kept at 30 °C. Chosen mobile phase for the analysis was acetonitrile: water at the pH (2.5) adjusted by orthophosphoric acid. The detection wavelength was selected as 237 nm. The linear relation for Dapsone and Adapalene was found in the range of 50–150 µg/mL and 1–3 µg/mL, respectively. The detection limit values for Dapsone and Adapalene were found to be 2.19 µg/mL and 0.10 µg/mL, respectively. While, the quantitation limit values were 6.64 µg/mL and 0.30 µg/mL, respectively, for Dapsone and Adapalene. For the precision studies % RSD values were found to be less than 2. The specificity of the method was verified by subjecting both the drugs to acid, alkali, oxidative, thermal degradation and photo stability studies. The developed method was validated by reaching satisfactory results for linearity, specificity, precision, accuracy, robustness and system suitability. The forced degradation studies concluded that, Dapsone was liable to degradation under all tested conditions except dry heat, whereas Adapalene was liable to degradation under all tested conditions except oxidation. Two well-resolved degradation products were generated by the oxidative degradation of Dapsone. Both the degradation products were isolated by preparative TLC and characterized by LC–MS. From the MS data probable structures of degradation products were proposed. From the above study it was suggested that Dapsone should be protected from oxidation during storage. © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.